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Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells

Steroids and growth factors control neuronal development through their receptors under physiological and pathological conditions. We show that PC12 cells harbor endogenous androgen receptor (AR), whose inhibition or silencing strongly interferes with neuritogenesis stimulated by the nonaromatizable...

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Detalles Bibliográficos
Autores principales: Di Donato, Marzia, Bilancio, Antonio, D'Amato, Loredana, Claudiani, Pamela, Oliviero, Maria Antonietta, Barone, Maria Vittoria, Auricchio, Alberto, Appella, Ettore, Migliaccio, Antimo, Auricchio, Ferdinando, Castoria, Gabriella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571344/
https://www.ncbi.nlm.nih.gov/pubmed/26063730
http://dx.doi.org/10.1091/mbc.E14-09-1352
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author Di Donato, Marzia
Bilancio, Antonio
D'Amato, Loredana
Claudiani, Pamela
Oliviero, Maria Antonietta
Barone, Maria Vittoria
Auricchio, Alberto
Appella, Ettore
Migliaccio, Antimo
Auricchio, Ferdinando
Castoria, Gabriella
author_facet Di Donato, Marzia
Bilancio, Antonio
D'Amato, Loredana
Claudiani, Pamela
Oliviero, Maria Antonietta
Barone, Maria Vittoria
Auricchio, Alberto
Appella, Ettore
Migliaccio, Antimo
Auricchio, Ferdinando
Castoria, Gabriella
author_sort Di Donato, Marzia
collection PubMed
description Steroids and growth factors control neuronal development through their receptors under physiological and pathological conditions. We show that PC12 cells harbor endogenous androgen receptor (AR), whose inhibition or silencing strongly interferes with neuritogenesis stimulated by the nonaromatizable synthetic androgen R1881 or NGF. This implies a role for AR not only in androgen signaling, but also in NGF signaling. In turn, a pharmacological TrkA inhibitor interferes with NGF- or androgen-induced neuritogenesis. In addition, androgen or NGF triggers AR association with TrkA, TrkA interaction with PI3-K δ, and downstream activation of PI3-K δ and Rac in PC12 cells. Once associated with AR, filamin A (FlnA) contributes to androgen or NGF neuritogenesis, likely through its interaction with signaling effectors, such as Rac. This study thus identifies a previously unrecognized reciprocal cross-talk between AR and TrkA, which is controlled by β1 integrin. The contribution of FlnA/AR complex and PI3-K δ to neuronal differentiation by androgens and NGF is also novel. This is the first description of AR function in PC12 cells.
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spelling pubmed-45713442015-10-16 Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells Di Donato, Marzia Bilancio, Antonio D'Amato, Loredana Claudiani, Pamela Oliviero, Maria Antonietta Barone, Maria Vittoria Auricchio, Alberto Appella, Ettore Migliaccio, Antimo Auricchio, Ferdinando Castoria, Gabriella Mol Biol Cell Articles Steroids and growth factors control neuronal development through their receptors under physiological and pathological conditions. We show that PC12 cells harbor endogenous androgen receptor (AR), whose inhibition or silencing strongly interferes with neuritogenesis stimulated by the nonaromatizable synthetic androgen R1881 or NGF. This implies a role for AR not only in androgen signaling, but also in NGF signaling. In turn, a pharmacological TrkA inhibitor interferes with NGF- or androgen-induced neuritogenesis. In addition, androgen or NGF triggers AR association with TrkA, TrkA interaction with PI3-K δ, and downstream activation of PI3-K δ and Rac in PC12 cells. Once associated with AR, filamin A (FlnA) contributes to androgen or NGF neuritogenesis, likely through its interaction with signaling effectors, such as Rac. This study thus identifies a previously unrecognized reciprocal cross-talk between AR and TrkA, which is controlled by β1 integrin. The contribution of FlnA/AR complex and PI3-K δ to neuronal differentiation by androgens and NGF is also novel. This is the first description of AR function in PC12 cells. The American Society for Cell Biology 2015-08-01 /pmc/articles/PMC4571344/ /pubmed/26063730 http://dx.doi.org/10.1091/mbc.E14-09-1352 Text en © 2015 Di Donato et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Di Donato, Marzia
Bilancio, Antonio
D'Amato, Loredana
Claudiani, Pamela
Oliviero, Maria Antonietta
Barone, Maria Vittoria
Auricchio, Alberto
Appella, Ettore
Migliaccio, Antimo
Auricchio, Ferdinando
Castoria, Gabriella
Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells
title Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells
title_full Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells
title_fullStr Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells
title_full_unstemmed Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells
title_short Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells
title_sort cross-talk between androgen receptor/filamin a and trka regulates neurite outgrowth in pc12 cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571344/
https://www.ncbi.nlm.nih.gov/pubmed/26063730
http://dx.doi.org/10.1091/mbc.E14-09-1352
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